Chronic heart failure (CHF) is manifested principally in the elderly population. Therefore, to understand the causes of exercise intolerance in CHF patients, it is imperative to resolve the effects of aging on muscle blood flow (BF) in CHF. To address this issue, we determined the muscle BF response to submaximal treadmill exercise (20 m/min, 5% grade) in young (Y(CHF): 6-8 mo, 412 +/- 11 g, n = 11) and old (O(CHF): 27-29 mo, 494 +/- 10 g, n = 8) Fischer 344 x Brown Norway rats with similar degrees of myocardial infarction-induced left ventricular (LV) dysfunction [resting LV end-diastolic pressure: Y(CHF) = 24 +/- 2, O(CHF) = 22 +/- 2 mmHg; derivative of LV pressure over time: Y(CHF) = 5,168 +/- 285; O(CHF) = 5,050 +/- 165 mmHg/s; lung weight normalized to body weight: Y(CHF) = 9.14 +/- 0.72; O(CHF) = 8.21 +/- 0.29 mg/g (all P > 0.05)]. The exercising heart rate response was blunted in O(CHF) compared with Y(CHF) rats (Y(CHF) = 454 +/- 8, O(CHF) = 395 +/- 9 beats/min; P < 0.05). BF (radiolabeled microspheres) to the total hindlimb musculature and to each of the 28 individual muscles examined was similar between Y(CHF) and O(CHF) rats under resting conditions. During exercise, BF to five of the hindlimb muscles that normally possess a majority of slow-twitch oxidative and fast-twitch oxidative glycolytic muscle fibers increased significantly less (-25 to -42%) for O(CHF) compared with Y(CHF) rats. In contrast, BF to 14 of the hindlimb muscles that normally possess a majority of fast-twitch glycolytic muscle fibers was increased (+22 to +337%) for O(CHF) vs. Y(CHF) rats, which contributed to a greater mass-specific total hindlimb BF response in O(CHF) rats (Y(CHF) = 78 +/- 5, O(CHF) = 100 +/- 11 ml.min(-1).100 g(-1); P < 0.05) and coincided with greater reductions in BF to the kidneys and splanchnic organs during exercise in O(CHF) vs. Y(CHF). In conclusion, there appears to be a profound age-related redistribution of BF from the highly oxidative to the highly glycolytic muscles of the hindlimb during exercise in O(CHF) compared with Y(CHF) rats. This phenomenon is qualitatively similar to that reported previously for healthy young and old rats.
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http://dx.doi.org/10.1152/japplphysiol.00896.2004 | DOI Listing |
J Org Chem
September 2024
Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland 20892-1003, United States.
A 2-phenyl-3-difluoromethoxy-pyridinyl moiety features in potent phosphodiesterase 4D inhibitors that are considered to be candidate radiotracers for positron emission tomography if they are labeled with fluorine-18. Fluorine-18 could be installed as desired at the 3'-phenyl position with acridinium-mediated photoredox radiodeoxyfluorination in homologues bearing variously substituted 3'-aryloxy groups. However, a distal 3-difluoromethoxide (-OCHF) group strongly competes as a leaving group, especially when an electron-deficient aryloxy group is present at position 3'.
View Article and Find Full Text PDFChemistry
November 2023
Institut für nachhaltige Chemie & Katalyse mit Bor (ICB) Institut für Anorganische Chemie, Julius-Maximimilians-Universität Würzburg, Am Hubland, 97074, Würzburg, Germany.
A scalable straightforward synthesis of monofluoro- and difluoromethyl triflate CF SO OCH F (M ) and CF SO OCHF (M ) through electrochemical fluorination (ECF, Simons process) of methyl triflate M in anhydrous hydrogen fluoride at nickel anodes is presented. The ECF method is also feasible for the preparation of the deuterated analogues CF SO OCD F (M ) and CF SO OCDF (M ). Surprisingly, no H/D exchange occurs during ECF of CF SO OCD (M ); this provides further evidence for a NiF /NiF -mediated ECF mechanism.
View Article and Find Full Text PDFJ Mol Graph Model
July 2023
Key Laboratory of Photoinduced Functional Materials, Mianyang Normal University, Mianyang, 621000, PR China. Electronic address:
The mechanism and dynamics of CHFCFOCHF initiated by OH radical evaluated through the density functional theory and variflex code. The solvation pattern of PCM was utilized to analyze the influence of water on the CHFCFOCHF + OH reaction. The most feasible reaction channel is resulting in the product CFCFOCHF with HO by hydrogen abstraction.
View Article and Find Full Text PDFJ Fluor Chem
April 2023
Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
This account describes our recent progress on the strategic incorporation of fluorine and organofluorine moieties into new-generation taxoid anticancer agents for medicinal chemistry and chemical biology studies. In the case study 1, novel 3rd-generation fluorotaxoids bearing 3-OCF or 3-OCFH group in the C2-benzoate moiety were designed, synthesized and examined for their anticancer activities. The potency of novel taxoids against drug-resistant cancer cell lines was 2-3 orders of magnitude higher than that of paclitaxel (PTX).
View Article and Find Full Text PDFOrg Lett
November 2022
Université de Strasbourg, Université de Haute-Alsace, CNRS, ECPM, UMR 7042-LIMA, 67000, Strasbourg, France.
We report herein the generation of difluoromethoxylated ketenimines. This novel intermediate is readily obtained from the corresponding oxime through a Beckmann rearrangement. The reactivity potential of this species is demonstrated as it easily undergoes addition of various nucleophiles, with a great modularity of the starting oxime.
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